University of South Florida

About: University of South Florida is a education organization based out in Tampa, Florida, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 34231 authors who have published 72644 publications receiving 2538044 citations. The organization is also known as: USF.

Behavioral Changes in Transgenic Mice Expressing Both Amyloid Precursor Protein and Presenilin-1 Mutations: Lack of Association with Amyloid Deposits

Abstract: Mutations in the amyloid precursor protein (mAPP) and in presenilin 1 (mPS1) have both been linked to increased production of the β-amyloid peptide (Aβ). Doubly transgenic mice produced by mating of a parental line carrying the “Swedish” (K670N/M671L) APP mutation with a FAD4 (M146L) mutant presenilin 1 line developed numerous fibrillar Aβ deposits by 6 months of age. Prior work demonstrated that mAPP and doubly transgenic (mAPP/mPS1) mice have deficits in Y-maze alternation behavior as early as 3 months of age. Increased activity was also apparent in the mAPP/mPS1 mice at this time point. These changes in Y-maze performance persisted in mAPP/mPS1 mice at 6 and 9 months of age. The mPS1 singly transgenic mice were not impaired on this task at any age. Six- and nine-month-old mice were also tested for spatial navigation behavior in the Morris water maze. In training trials, no differences in escape latency were detected among the four genotypes. In probe trials, no differences were detected in either the time spent in the trained quadrant or the number of platform crossings among the four groups. Histological staining for Aβ amyloid deposits indicates that all doubly transgenic mice have amyloid deposits by 6 months of age (roughly 25 mice examined thus far), yet no 3-month-old mice have been found with deposits. Aβ immunostaining confirmed that the 9-month-old mice tested behaviorally also have Aβ deposits. Thus, doubly transgenic mice exhibited changes in Y-maze performance prior to the formation of amyloid deposits, which are essentially unchanged as the deposits increase in number and size to 9 months of age. Yet these mice fail to reveal impairments in spatial navigation at 6 or 9 months in spite of the increasing plaque burden. These data indicate that Aβ deposits alone are not sufficient to cause robust spatial memory impairment in mice of this mixed background lineage and age.

Nivolumab in Combination With Platinum-Based Doublet Chemotherapy for First-Line Treatment of Advanced Non-Small-Cell Lung Cancer.

Abstract: PurposeNivolumab, a fully human immunoglobulin G4 programmed death-1 immune checkpoint inhibitor antibody, has demonstrated improved survival in previously treated patients with advanced non–small-cell lung cancer (NSCLC). CheckMate 012, a phase I, multicohort study, was conducted to explore the safety and efficacy of nivolumab as monotherapy or combined with current standard therapies in first-line advanced NSCLC. Here, we report results for nivolumab plus platinum-based doublet chemotherapy (PT-DC).Patients and MethodsPatients (N = 56) received nivolumab (intravenously) plus PT-DC concurrently every 3 weeks for four cycles followed by nivolumab alone until progression or unacceptable toxicity. Regimens were nivolumab 10 mg/kg plus gemcitabine-cisplatin (squamous) or pemetrexed-cisplatin (nonsquamous) or nivolumab 5 or 10 mg/kg plus paclitaxel-carboplatin (all histologies). The primary objective was to assess safety and tolerability. Secondary objectives included objective response rate and 24-week progr...

Selective predisposition to bacterial infections in IRAK-4–deficient children: IRAK-4–dependent TLRs are otherwise redundant in protective immunity

Abstract: Human interleukin (IL) 1 receptor-associated kinase 4 (IRAK-4) deficiency is a recently discovered primary immunodeficiency that impairs Toll/IL-1R immunity, except for the Toll-like receptor (TLR) 3- and TLR4-interferon (IFN)-alpha/beta pathways. The clinical and immunological phenotype remains largely unknown. We diagnosed up to 28 patients with IRAK-4 deficiency, tested blood TLR responses for individual leukocyte subsets, and TLR responses for multiple cytokines. The patients' peripheral blood mononuclear cells (PBMCs) did not induce the 11 non-IFN cytokines tested upon activation with TLR agonists other than the nonspecific TLR3 agonist poly(I:C). The patients' individual cell subsets from both myeloid (granulocytes, monocytes, monocyte-derived dendritic cells [MDDCs], myeloid DCs [MDCs], and plasmacytoid DCs) and lymphoid (B, T, and NK cells) lineages did not respond to the TLR agonists that stimulated control cells, with the exception of residual responses to poly(I:C) and lipopolysaccharide in MDCs and MDDCs. Most patients (22 out of 28; 79%) suffered from invasive pneumococcal disease, which was often recurrent (13 out of 22; 59%). Other infections were rare, with the exception of severe staphylococcal disease (9 out of 28; 32%). Almost half of the patients died (12 out of 28; 43%). No death and no invasive infection occurred in patients older than 8 and 14 yr, respectively. The IRAK-4-dependent TLRs and IL-1Rs are therefore vital for childhood immunity to pyogenic bacteria, particularly Streptococcus pneumoniae. Conversely, IRAK-4-dependent human TLRs appear to play a redundant role in protective immunity to most infections, at most limited to childhood immunity to some pyogenic bacteria.

Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and the Endocrine Society.

Abstract: Objective: To review the evidence about the impact of hypoglycemia on patients with diabetes that has become available since the past reviews of this subject by the American Diabetes Association and The Endocrine Society and to provide guidance about how this new information should be incorporated into clinical practice. Participants: Five members of the American Diabetes Association and five members of The Endocrine Society with expertise in different aspects of hypoglycemia were invited by the Chair, who is a member of both, to participate in a planning conference call and a 2-day meeting that was also attended by staff from both organizations. Subsequent communications took place via e-mail and phone calls. The writing group consisted of those invitees who participated in the writing of the manuscript. The workgroup meeting was supported by educational grants to the American Diabetes Association from Lilly USA, LLC and Novo Nordisk and sponsorship to the American Diabetes Association from Sanofi. The s...